It is proposed to continue studies in animals concerned with cerebral metabolism (CMR) and cerebral blood flow (CBF) with particular emphasis on the impact of anesthetic agents and techniques on both normal and ischemic brain. CBF will be measured by a direct venous outflow method and CMRO2 and CMR glucose will be calculated from simultaneous measurements of CBF and arterial-sagittal sinus blood content differences. The cerebral energy state will also be evaluated by measuring cerebral tissue levels of ATP, phosphocreatine, lactate, and pyruvate. In studies of regional cerebral ischemia, the effect of middle cerebral artery (MCA) occlusion on the cerebral energy state, neurologic function, and size of infarction will be evaluated in squirrel and Java monkeys in the presence and absence of such proposed therapeutic measures as barbiturate anesthesia, halothane anesthesia, hypothermia, hypocapnia, and hypertension. By these means, it is intended to identify those therapeutic measures which do have clinical application in the management of acute stroke. In dogs supported by extracorporeal circulation, we will examine the cerebral metabolic effects of massive anesthetic concentrations in order to unmask any potential cerebral toxic effects and determine at what concentration such effects occur. In dogs, we propose to explore the cerebral metabolic effects of hypoglycemia in order to determine whether the cerebral energy state remains unaffected even in the presence of neurologic dysfunction and altered CMRO2. In pigs, the effect of malignant hyperthermia on cerebral metabolism will be examined and the "critical" temperature for irreversible brain damage determined. In dogs, the cerebral metabolic and vascular effects of any new anesthetics introduced during the period of this proposal will be studied.